Background: The atopic march hypothesis suggests that infants with eczema are at increased risk of asthma. Others argue that eczema is not a risk factor for asthma unless there is also sensitization or early wheezing. Objective: To examine the role of infantile eczema as a predictor of risk of childhood asthma, while allowing for the effects of early wheeze, sensitization, and sex, both as independent effects and possible effect modifiers. Methods: A total of 620 infants with a family history of allergic disease was recruited. Eczema and wheeze was prospectively documented to 2 years of age. Sensitization was determined by skin prick tests at 6, 12, and 24 months to 6 common food and inhalant allergens. Interviews were conducted at 6 and 7 years to ascertain current asthma. Results: Sufficiently complete data were available for 403 children. Eczema within the first 2 years of life was clearly associated with an increased risk of childhood asthma in boys (adjusted odds ratio, 2.45; 95% CI, 1.31-4.46) but not in girls (odds ratio, 0.88; 95% CI, 0.43-1.77; P for interaction = .031) even with adjustment for the effects of early allergic sensitization and wheeze. If these relationships are causal, an intervention to prevent eczema in boys might reduce the incidence of childhood asthma by as much as 28%. Conclusion: Eczema in the first 2 years of life is associated with an increased risk of childhood asthma in boys, but there is no evidence of this in girls.